# Patent

## Title
Microbicide combinations containing silver

## Abstract

A synergistic microbicidal composition. The composition comprises a silver-containing copolymer comprising polymerized units of a monomer X and a monomer Y; wherein monomer X is an ethylenically unsaturated compound having a substituent group selected from an unsaturated or aromatic heterocyclic group having at least one hetero atom selected from N, O and S; wherein monomer Y is selected from carboxylic acids, carboxylic acid salts, carboxylic acid esters, organosulfuric acids, organosulfuric acid salts, sulfonic acids, sulfonic acid salts, phosphonic acids, phosphonic acid salts, vinyl esters, (meth)acrylamides, C8-C20 aromatic monomers containing at least one exocyclic ethylenic unsaturation and combinations thereof; and at least one organic biocide.

## Background
This application claims the benefit of priority under 35 U.S.C. §119(e) of U.S. Provisional Patent Application No. 60/858,848 filed on Nov. 14, 2006.


The present invention relates to microbicide combinations containing silver, and in particular to combinations of organic biocides with polymers complexed with silver ion.
A silver-containing copolymer having monomer units derived from vinylpyridine is disclosed in Japanese Kokai H11-222402. However, this reference does not teach combinations of this copolymer with other biocidal agents.
Use of combinations of at least two antimicrobial compounds can broaden potential markets, reduce use concentrations and costs, and reduce waste. In some cases, commercial antimicrobial compounds cannot provide effective control of microorganisms, even at high use concentrations, due to weak activity against certain types of microorganisms, e.g., those resistant to some antimicrobial compounds. Combinations of different antimicrobial compounds are sometimes used to provide overall control of microorganisms in a particular end use environment. The problem addressed by this invention is to provide such synergistic combinations of antimicrobial compounds.


The present invention is directed to a synergistic microbicidal composition. The composition comprises: (a) a silver-containing copolymer comprising polymerized units of a monomer X and a monomer Y; wherein monomer X is an ethylenically unsaturated compound having a substituent group selected from an unsaturated or aromatic heterocyclic group having at least one hetero atom selected from N, O and S; alternatively the substituent group is selected from an unsaturated or aromatic heterocyclic group having at least one hetero N atom; and wherein monomer Y is an ethylenically unsaturated compound selected from carboxylic acids, carboxylic acid salts, carboxylic acid esters, organosulfuric acids, organosulfuric acid salts, sulfonic acids, sulfonic acid salts, phosphonic acids, phosphonic acid salts, vinyl esters, (meth)acrylamides, C8-C20 aromatic monomers containing at least one exocyclic ethylenic unsaturation and combinations thereof; and (b) 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one, 2-n-octyl-4-isothiazolin-3-one, 5-chloro-2-methyl-4-isothiazolin-3-one, 2-methyl-4-isothiazolin-3-one, C12-C16 alkyl dimethylbenzylammonium chloride, diisobutylphenoxyethoxyethyl dimethylbenzylammonium chloride, C9-C15 alkyltolylmethy trimethylammonium chloride, benzisothiazolin-3-one, hydrogen peroxide, sodium hypochlorite, glutaraldehyde, 5-chloro-2-(2,4-dichlorophenoxy)phenol, 3-iodo-2-propynylbutyl carbamate or a combination thereof.
The term “copolymer” as used herein and in the appended claims refers to polymers polymerized from at least two different monomers. Percentages herein are by weight, unless specified otherwise. Monomer unit percentages are based on total copolymer weight.
The term “aqueous” as used herein and in the appended claims means water and mixtures composed substantially of water and water miscible solvents.
The use of the term “(meth)” followed by another term such as acrylic, acrylate, acrylamide, etc., as used herein and in the appended claims, refers to, for example, both acrylic and methacrylic; acrylate and methacrylate; acrylamide and methacrylamide; etc.
The glass transition temperature (“Tg”) for the copolymers and pressure sensitive adhesive formulations of the present invention may be measured by differential scanning calorimetry (DSC) taking the mid-point in the heat flow versus temperature transition as the Tg value.
In some embodiments of the present invention, the copolymer comprises at least 15 wt % of monomer X derived units. In some aspects of these embodiments, the copolymer comprises at least 20 wt % of monomer X derived units. In some aspects of these embodiments, the copolymer comprises at least 25 wt % of monomer X derived units. In some aspects of these embodiments, the copolymer comprises at least 30 wt % of monomer X derived units. In some aspects of these embodiments, the copolymer comprises at least 35 wt % of monomer X derived units, alternatively at least 40 wt %. In some aspects of these embodiments, the copolymer comprises no more than 60 wt % of monomer X derived units, alternatively no more than 55 wt %, alternatively no more than 50 wt %.
In some embodiments of the present invention, monomer X is selected from vinylimidazoles, vinylimidazolines, vinylpyridines, vinylpyrroles, derivatives thereof and combinations thereof. In some aspects of these embodiments, monomer X is selected from vinylimidazoles, vinylpyridines, derivatives thereof and combinations thereof. In some aspects of these embodiments, monomer X is selected from N-vinylimidazole, 2-vinylpyridine, 4-vinylpyridine and combinations thereof. In some aspects of these embodiments, monomer X is N-vinylimidazole (VI).
In some embodiments of the present invention, monomer Y is selected from carboxylic acids, carboxylic acid salts, carboxylic acid esters, organosulfuric acids, organosulfuric acid salts, sulfonic acids, sulfonic acid salts, phosphonic acids, phosphonic acid salts, vinyl esters, (meth)acrylamides, C8-C20 aromatic monomers containing at least one exocyclic ethylenic unsaturation and combinations thereof. In some aspects of these embodiments, monomer Y is selected from carboxylic acids, carboxylic acid esters (e.g., alkyl (meth)acrylates), (meth)acrylamides, C8-C20 aromatic monomers containing at least one exocyclic ethylenic unsaturation and combinations thereof. In some aspects of these embodiments, monomer Y is selected from acrylic acid (AA), methacrylic acid, itaconic acid, maleic acid, fumaric acid, methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, isopropyl acrylate, n-butyl (meth)acrylate, isobutyl (meth)acrylate, 2-ethylhexyl (meth)acrylate, decyl (meth)acrylate, lauryl (meth)acrylate, stearyl (meth)acrylate, styrene, vinyltoluene, α-methylstyrene and combinations thereof. In some aspects of these embodiments, monomer Y comprises at least one C2-C8 alkyl (meth)acrylate, alternatively n-butyl (meth)acrylate, alternatively monomer Y comprises n-butyl acrylate (BA) and acrylic acid.
In some embodiments of the present invention, the method uses a copolymer comprising polymerized units of a monomer X and a monomer Y; wherein the copolymer comprises at least 15 wt % of monomer X derived units; wherein monomer X is selected from vinylimidazoles, vinylimidazolines, vinylpyridines, vinylpyrroles, derivatives thereof and combinations thereof; and wherein monomer Y is selected from carboxylic acids, carboxylic acid salts, carboxylic acid esters, organosulfuric acids, organosulfuric acid salts, sulfonic acids, sulfonic acid salts, phosphonic acids, phosphonic acid salts, vinyl esters, (meth)acrylamides, C8-C20 aromatic monomers containing at least one exocyclic ethylenic unsaturation and combinations thereof; and with the proviso that the composition comprises no more than 5 wt % of units derived from ethylenically unsaturated monomer containing an epoxide function. In some aspects of these embodiments, the copolymer comprises no more than 1 wt % of units derived from ethylenically unsaturated monomer containing an epoxide function. In some aspects of these embodiments, the copolymer comprises no more than 0.5 wt % of units derived from ethylenically unsaturated monomer containing an epoxide function. In some aspects of these embodiments, the copolymer comprises no more than 0.1 wt % of units derived from ethylenically unsaturated monomer containing an epoxide function. In some aspects of these embodiments, the copolymer comprises no more than 0.05 wt % of units derived from ethylenically unsaturated monomer containing an epoxide function.
In some embodiments of the present invention, the composition comprising a copolymer has a pH of at least 7. In some aspects of these embodiments, the composition has a pH of 7-10. In some aspects of these embodiments, the composition has a pH of at least 8. In some aspects of these embodiments, the composition has a pH of 8-10. In some aspects of these embodiments, the composition has a pH of at least 9. In some aspects of these embodiments, the composition has a pH of 9-10.
In some embodiments of the present invention, the composition comprising a copolymer comprises at least 20 wt % solids. In some aspects of these embodiments, the composition comprises at least 25 wt % solids. In some aspects of these embodiments, the composition comprises at least 30 wt % solids.
In some embodiments of the present invention, the composition comprises from 35 to 55 wt % of polymerized units derived from monomer X and 45 to 65 wt % of polymerized units derived from monomer Y. In some aspects of these embodiments, the composition comprises from 40 to 50 wt % of polymerized units derived from monomer X and 50 to 60 wt % of polymerized units derived from monomer Y.
In some embodiments of the present invention, the composition comprises polymerized units derived from a crosslinker. Crosslinkers suitable for use with the present invention include multi-ethylenically unsaturated monomers. In some aspects of these embodiments, the crosslinker derived units are derived from crosslinker selected from 1,4-butanediol diacrylate; 1,4-butanediol dimethacrylate; 1,6-hexanediol diacrylate; 1,1,1-trimethylol propane triacrylate; 1,1,1-trimethylol propane trimethacrylate; allyl methacrylate; divinylbenzene; and N-allyl acrylamide. In some aspects of these embodiments, the crosslinker derived units are derived from crosslinker selected from 1,1,1-trimethylol propane trimethacrylate. In some aspects of these embodiments, the composition comprises 0.01 to 10 wt % (based on solids) crosslinker. In some aspects of these embodiments, the composition comprises 0.01 to 5 wt % (based on solids) crosslinker. In some aspects of these embodiments, the composition comprises 0.01 to 1 wt % (based on solids) crosslinker.
In one embodiment of the invention, the copolymer comprises from 1.5 wt % to 20 wt % silver based on total weight of copolymer and silver, alternatively from 2.5 wt % to 15 wt %, alternatively from 5 wt % to 11.5 wt %, alternatively from 6.5 wt % to 8.5 wt %. Silver is in the form of Ag(I) ion, which typically is introduced in the form of silver nitrate. Methods for preparation of the copolymer have been disclosed previously, e.g., in U.S. Pat. Appl. Pub. No. US 2005/0227895.
In one embodiment of the invention, the antimicrobial composition comprises a silver-containing copolymer; and 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT). Preferably, a weight ratio of silver to DCOIT is from 1:0.014 to 1:20, more preferably from 1:0.014 to 1:15.
In one embodiment of the invention, the antimicrobial composition comprises a silver-containing copolymer; and 2-n-octyl-4-isothiazolin-3-one (OIT). Preferably, a weight ratio of silver to OIT is from 1:0.039 to 1:8360.
In one embodiment of the invention, the antimicrobial composition comprises a silver-containing copolymer; and a 3:1 mixture of 5-chloro-2-methyl-4-isothiazolin-3-one (CMIT) and 2-methyl-4-isothiazolin-3-one (MIT). Preferably, a weight ratio of silver to the CMIT/MIT mixture is from 1:0.039 to 1:140.
In one embodiment of the invention, the antimicrobial composition comprises a silver-containing copolymer; and MIT. Preferably, a weight ratio of silver to MIT is from 1:39.2 to 1:3020.
In one embodiment of the invention, the antimicrobial composition comprises a silver-containing copolymer; and C12-C16 alkyl dimethylbenzylammonium chloride. Preferably, a weight ratio of silver to C12-C16 alkyl dimethylbenzylammonium chloride is from 1:7.76 to 1:1000, more preferably from 1:32 to 1:980.
In one embodiment of the invention, the antimicrobial composition comprises a silver-containing copolymer; and diisobutylphenoxyethoxyethyl dimethylbenzylammonium chloride. Preferably, a weight ratio of silver to diisobutylphenoxyethoxyethyl dimethylbenzylammonium chloride is from 1:1.94 to 1:576.
In one embodiment of the invention, the antimicrobial composition comprises a silver-containing copolymer; and C9-C15 alkyltolylmethyltrimethylammonium chloride. Preferably, a weight ratio of silver to C9-C15 alkyltolylmethyltrimethylammonium chloride is from 1:26 to 1:6040.
In one embodiment of the invention, the antimicrobial composition comprises benzisothiazolin-3-one and a silver-containing copolymer. Preferably, a weight ratio of benzisothiazolin-3-one to silver is from 1:0.0002 to 1:1.
In one embodiment of the invention, the antimicrobial composition comprises hydrogen peroxide and a silver-containing copolymer. Preferably, a weight ratio of hydrogen peroxide to silver is from 1:0.000005 to 1:0.01.
In one embodiment of the invention, the antimicrobial composition comprises sodium hypochlorite and a silver-containing copolymer. Preferably, a weight ratio of sodium hypochlorite to silver is from 1:0.008 to 1:200.
In one embodiment of the invention, the antimicrobial composition comprises glutaraldehyde and a silver-containing copolymer. Preferably, a weight ratio of glutaraldehyde to silver is from 1:0.00006 to 1:0.047.
In one embodiment of the invention, the antimicrobial composition comprises 5-chloro-2-(2,4-dichlorophenoxy)phenol and a silver-containing copolymer. Preferably, a weight ratio of 5-chloro-2-(2,4-dichlorophenoxy)phenol to silver is from 1:0.00011 to 1:0.57.
In one embodiment of the invention, the antimicrobial composition comprises 3-iodo-2-propynylbutyl carbamate and a silver-containing copolymer. Preferably, a weight ratio of 3-iodo-2-propynylbutyl carbamate to silver is from 1:0.000002 to 1:80.
The specific amount of the composition of this invention necessary to inhibit or control the growth of microorganisms in an application will vary. Typically, the amount of the composition of the present invention is sufficient to control the growth of microorganisms if it provides from 0.1 to 25,000 ppm (parts per million) active ingredient of the composition (as silver plus co-biocide combined). It is preferred that the active ingredients of the composition be present in the locus in an amount of at least 0.1 ppm, more preferably at least 5 ppm, more preferably at least 50 ppm and most preferably at least 500 ppm. In one embodiment of the invention, the active ingredients are present in an amount of at least 2,000 ppm. It is preferred that the active ingredients of the composition be present in the locus in an amount of no more than 20,000 ppm, more preferably no more than 15,000 ppm, more, preferably no more than 5,000 ppm. In one embodiment of the invention, the active ingredients are present in an amount of no more than 15,000 ppm, more preferably no more than 8,000 ppm, and most preferably no more than 3,000 ppm.
Some embodiments of the present invention will now be described in detail in the following Examples. The silver-containing copolymer tested in these Examples comprises a polymer having 45% BA monomer units, 45% VI monomer units and 10% AA monomer units, based on polymer weight, and containing 7.8% silver ion, based on total weight of polymer and silver. The silver-containing polymer was formulated in water at 39% solids and pH 11.
The synergism of the combination of the present invention was demonstrated by testing a wide range of concentrations and ratios of the compounds.
One measure of synergism is the industrially accepted method described by Kull, F. C.; Eisman, P. C.; Sylwestrowicz, H. D. and Mayer, R. L., in Applied Microbiology 9:538-541 (1961), using the ratio determined by the formula: Ca/CA+Cb/CB=Synergy Index (“SI”) wherein:
CA=concentration of compound A (first component) in ppm, acting alone, which produced an end point (MIC of Compound A).
Ca=concentration of compound A in ppm, in the mixture, which produced an end point.
CB=concentration of compound B (second component) in ppm, acting alone, which produced an end point (MIC of Compound B).
Cb=concentration of compound B in ppm, in the mixture, which produced an end point.
When the sum of Ca/CA and Cb/CB is greater than one, antagonism is indicated. When the sum is equal to one, additivity is indicated, and when less than one, synergism is demonstrated. The lower the SI, the greater the synergy shown by that particular mixture. The minimum inhibitory concentration (MIC) of an antimicrobial compound is the lowest concentration tested under a specific set of conditions that prevents the growth of added microorganisms.
Synergy tests were conducted using standard microtiter plate assays with media designed for optimal growth of the test microorganism. Soybean Casein Digest Broth (Tryptic Soy Broth, TSB medium) or minimal salt medium supplemented with 0.2% glucose and 0.1% yeast extract (M9GY medium) was used for testing bacteria; Potato Dextrose Broth (PDB medium) was used for testing yeast and mold. In this method, a wide range of combinations of microbicides was tested by conducting high resolution MIC assays in the presence of various concentrations of the biocides. High resolution MICs were determined by adding varying amounts of microbicide to one column of a microtitre plate and doing subsequent ten-fold dilutions using an automated liquid handling system.
The synergy of the combinations of the present invention was determined against four bacteria, gram positive Staphylococcus aureus (S. aureus—ATCC #6538) and gram negative Pseudomonas aeruginosa (P. aeruginosa—ATCC #15442), Samonella choleraesuis (S. choleraesuis—ATCC #10708) and Esherichia coli (E. coli—ATCC #8739), a yeast, Candida albicans (C. albicans—ATCC 10231), and a mold, Aspergillus niger (A. niger—ATCC 16404). The bacteria were used at a concentration of about 1-6×106 bacteria per mL and the yeast and mold at 1-5×105 fungi per mL. These microorganisms are representative of natural contaminants in many consumer and industrial applications. The plates were visually evaluated for microbial growth (turbidity) to determine the MIC after various incubation times at 25° C. (yeast and mold) or 30° C. (bacteria).
The test results for demonstration of synergy of the microbicide combinations of the present invention are shown below in the Tables. Each table shows the specific combinations of component (a) and the second component (b); results against the microorganisms tested with incubation times; the end-point activity in ppm measured by the MIC for Component (a) (Ca), for the second component alone (Cb), for the mixture (Ca) and for second component in the mixture (Cb); the calculated SI value; and the range of synergistic ratios for each combination tested (first component/second component or a+b). The end point values in the following examples for the silver-polymer complex are reported on an active silver ion basis.












TABLE 1





Test Organisms
Contact Time
Ca
Cb
S.I.
Ca:Cb




















S. choleraesuis
24 hour
0.1
—
—



ATCC # 10708

—
0.3
—




0.01
0.2
0.77
1:20




0.025
0.2
0.92
1:8


S. aureus
24 hour
0.5
—
—


ATCC # 6538)

—
 0.99
—




0.01
 0.81
0.84
1:81




0.025
 0.58
0.64
1:23.2




0.1
 0.58
0.79
1:5.8




0.15
0.2
0.5 
1:1.33




0.25
 0.16
0.66
1:0.64



48 hour
0.5
—
—




—
 0.99
—




0.01
1  
0.73
1:100




0.025
0.8
0.62
1:32




0.1
 0.58
0.61
1:5.8




0.15
0.2
0.44
1:1.33




0.25
 0.16
0.61
1:0.64


E. coli
24 hour
0.25
—
—


ATCC # 8739

—
1.2
—




0.01
1  
0.87
1:100




0.05
0.8
0.87
1:16




0.1
0.8
1.07
1:8




0.15
 0.16
0.73
1:1.07



48 hour
0.25
—
—




—
1.6
—




0.01
1.4
0.92
1:140




0.025
1.4
0.98
1:56




0.15
0.2
0.73
1:1.33


C. albicans
24 hour
5
—
—


ATCC # 10231

—
1.6
—




2.5
1.9
1.01
1:0.76



48 hour
10
—
—




—
3.9
—




2.5
1.6
0.66
1:0.64




5
1.6
0.91
1:0.32


A. niger
 3 days
5
—
—


ATCC # 16404

—
3.9
—




2.5
 1.96
1.01
1:0.78



 7 days
20
—
—




—
3.9
—




5
 1.21
0.56
1:0.24




10
 0.99
0.76
1:0.1




15
 0.58
0.9 
1:0.039





Ca = Component A (Ag-polymer formulation)


Cb = Component B (CMIT/MIT)


















TABLE 2





Test Organisms
Contact Time
Ca
Cb
S.I.
Ca:Cb




















P. aeruginosa
24 hour
0.1
—
—



ATCC # 15442

—
443.5
—




0.025
361
1.06
1:14440


S. choleraesuis
24 hour
0.1
—


ATCC # 10708

—
361




0.05
209
1.08
1:4180



48 hour
0.1
—




—
361




0.05
209
1.08
1:4180


S. aureus
24 hour
0.5
—
—


ATCC # 6538

—
72.8
—




0.025
58.8
0.86
1:2352




0.1
58.8
1.01
1:588




0.15
50.8
1  
1:338.7



48 hour
0.5
—
—




—
72.8
—




0.01
72.8
1.02
1:7280




0.025
72.8
1.05
1:2912


E. coli
24 hour
0.25
—
—


ATCC # 9739

—
294
—




0.01
294
1.04
1:29400




0.025
209
0.81
1:8360




0.05
209
0.91
1:4180




0.1
141
0.88
1:1410




0.15
141
1.08
1:940



48 hour
0.25
—
—




—
294
—




0.01
294
1.04
1:29400




0.05
209
0.91
1:4180


C. albicans
24 hour
5
—
—


ATCC # 10231

—
0.81
—




2.5
0.39
0.98
1:0.156




2.5
0.2
0.75
1:0.08




2.5
0.16
0.70
1:0.064



48 hour
0.25
—
—




—
0.99
—




2.5
0.58
0.84
1:0.232




2.5
0.39
0.64
1:0.156


A. niger
 3 days
5
—
—


ATCC # 16404

—
3.9
—




2.5
1.59
0.91
1:0.636




2.5
1.38
0.86
1:0.552



 7 days
20
—
—




—
5.76
—




2.5
1.96
0.47
1:0.784




5
1.21
0.46
1:0.242




10
0.99
0.67
1:0.1




15
0.58
0.85
1:0.039





Ca = Component A (Ag-polymer formulation)


Cb = Component B (OIT)


















TABLE 3





Test-Organisms
Contact Time
Ca
Cb
S.I.
Ca:Cb




















P. aerginosa
48 hour
0.1
—
—
—


ATCC # 15442

—
24.7
—
—




0.01
20.2
0.92
1:2020




0.025
20.2
1.07
1:808


S. aureus
24 hour
0.5
—
—


ATCC # 6538

—
34.5
—




0.01
30.2
0.9 
1:3020




0.025
30.2
0.93
1:1208




0.1
24.7
0.92
1:247




0.15
24.7
1.02
1:164.67




0.25
14.4
0.92
1:57.6



48 hour
0.5
—
—




—
34.5
—




0.01
34.5
1.02
1:3450




0.025
34.5
1.05
1:1380




0.1
30.2
1.08
1:302




0.25
14.4
0.92
1:57.6


C. albicans
24 hour
5
—
—


ATCC # 10231

—
288
—




2.5
98
0.84
1:39.2



48 hour
10
—
—




—
403
—




2.5
288
0.96
1:115.2




5
194
0.98
1:38.8


A. niger
 3 days
5
—
—


ATCC # 16404

—
493
—




2.5
288
1.08
1:115.2



 7 days
20
—
—




—
603
—




5
493
1.07
1:98.6




10
288
0.98
1:28.8




15
98
0.91
1:6.53





Ca = Component A (Ag-polymer formulation)


Cb = Component B (MIT)


















TABLE 4





Test Organisms
Contact Time
Ca
Cb
S.I.
Ca:Cb




















P. aerginosa
 24 hour
0.1
—
—



ATCC # 15442

—
1.5
—




0.01
1.47
1.08
1:147



48 hour
0.1
—
—




—
2.9
—




0.05
0.29
0.91
1:5.8


S. choleraesuis
248 hour
0.1
—
—


ATCC # 10708

—
1.5
—




0.05
0.29
0.69
1:5.8


S. aureus
 24 hour
0.5
—
—


ATCC # 6538

—
0.29
—




0.01
0.1
0.36
1:10




0.025
0.1
0.39
1:4




0.05
0.1
0.44
1:2




0.1
0.07
0.44
1:0.7




0.15
0.04
0.44
1:0.27




0.25
0.04
0.64
1:0.16



 48 hour
0.5
—
—




—
0.29
—




0.01
0.15
0.54
1:15




0.025
0.15
0.57
1:6




0.05
0.15
0.62
1:3




0.1
0.07
0.44
1:0.7




0.15
0.06
0.51
1:0.4




0.25
0.06
0.71
1:0.24


E. coli
 24 hour
0.25
—
—


ATCC # 9739

—
0.29
—




0.01
0.1
0.38
1:10




0.025
0.07
0.34
1:2.8




0.05
0.07
0.44
1:1.4




0.1
0.06
0.61
1:0.6




0.15
0.04
0.74
1:0.27



 48 hour
0.25
—
—




—
0.43
—




0.01
0.1
0.27
1:10




0.025
0.1
0.33
1:4




0.05
0.07
0.36
1:1.4




0.1
0.06
0.54
1:0.6




0.15
0.06
0.74
1:0.4


C. albicans
 48 hour
10
—
—
—


ATCC # 10231

—
0.15
—
—




2.5
0.07
0.72
1:0.028




5
0.07
0.97
1:0.014


A. niger
 7 days
20
—
—
—


ATCC # 16404

—
2
—
—




2.5
1
0.63
1:0.4




5
0.7
0.6 
1:0.14




10
0.7
0.85
1:0.07




15
0.48
0.99
1:0.03





Ca = Component A (Ag-polymer formulation)


Cb = Component B (DCOIT)


















TABLE 5





Test Organisms
Contact Time
Ca
Cb
S.I.
Ca:Cb




















S. choleraesuis
48 hour
0.1
—
—



ATCC # 10708

—
6.9
—




0.01
6
0.97
1:600


S. aureus
24 hour
0.5
—
—


ATCC # 6538

—
19.4
—




0.01
9.8
0.53
1:980




0.025
9.8
0.56
1:392




0.05
4.9
0.35
1:98




0.1
4.9
0.45
1:49




0.15
4.9
0.55
1:32.67




0.25
4.9
0.75
1:19.6



48 hour
0.5
—
—




—
19.4
—




0.01
19.4
1.02
1:1940




0.025
19.4
1.05
1:776




0.05
9.8
0.61
1:196




0.1
9.8
0.71
1:98




0.15
8
0.71
1:53.33




0.25
8
0.91
1:32


E. coli
48 hour
0.25
—
—


ATCC # 9739

—
4.9
—




0.01
4.9
1.04
1:490




0.025
4
0.92
1:160




0.05
4
1.02
1:80


C. albicans
24 hour
5
—
—


ATCC # 10231

—
40.3
—




2.5
19.4
0.98
1:7.76



48 hour
10
—
—




—
98
—




2.5
60.4
0.87
1:24.16




5
49
1  
1:9.8


A. niger
 3 days
5
—
—


ATCC # 16404

—
194
—




2.5
80
0.91
1:32



 7 days
20
—
—




—
603
—




5
194
0.92
1:38.8




15
98
1.09
1:6.53





Ca = Component A (Ag-polymer formulation)


Cb = Component B (C12-C16 alkyl dimethylbenzylammonium chloride)


















TABLE 6





Test Organisms
Contact Time
Ca
Cb
S.I.
Ca:Cb




















S. aureus
24 hour
0.5
—
—



ATCC # 6538

—
28.8
—




0.01
28.8
1.02
1:2880




0.025
28.8
1.05
1:1152




0.15
28.8
0.97
1:192



48 hour
0.5
—
—




—
40.3
—




0.01
40.3
1.02
1:4030




0.025
40.3
1.05
1:1612




0.05
28.8
0.81
1:576




0.1
28.8
0.91
1:288




0.15
28.8
1.01
1:192


E. coli
24 hour
0.25
—
—


ATCC # 9739

—
19.4
—




0.01
19.4
1.04
1:1940




0.1
 9.8
0.91
1:98




0.15
 4.9
0.85
1:32.67


C. albicans
48 hour
10
—
—


ATCC # 10231

—
28.8
—




2.5
19.4
0.92
1:7.76


A. niger
 7 days
20
—
—


ATCC # 16404

—
40.3
—




5
28.8
0.96
1:5.76




10
19.4
0.98
1:1.94





Ca = Component A (Ag-polymer formulation)


Cb = Component B (diisobutylphenoxyethoxyethyl dimethylbenzylammonium chloride)


















TABLE 7





Test Organisms
Contact Time
Ca
Cb
S.I.
Ca:Cb




















P. aeruginosa
24 hour
0.1
—
—



ATCC # 15442

—
19.4
—




0.025
9.8
0.76
1:392




0.05
9.8
1.01
1:196



48 hour
0.1
—
—




—
19.4
—




0.025
9.8
0.76
1:392




0.05
9.8
1.01
1:196


S. aureus
24 hour
0.5
—
—


ATCC # 6538

—
69
—




0.01
60.4
0.9 
1:6040




0.025
28.8
0.47
1:1152




0.05
28.8
0.52
1:576




0.1
9.8
0.34
1:98




0.15
9.8
0.44
1:65.33




0.25
9.8
0.64
1:39.2



48 hour
0.5
—
—




—
69
—




0.01
69
1.02
1:6900




0.025
28.8
0.47
1:1152




0.05
28.8
0.52
1:576




0.1
19.4
0.48
1:194




0.15
19.4
0.58
1:129.33




0.25
19.4
0.78
1:77.6



48 hour
4
—
—




—
44
—




1
26
0.84
1:26




1
33
1  
1:33




2
26
1.09
1:13


E. coli
24 hour
0.25
—
—
—


ATCC # 9739

—
6
—
—




0.01
4.9
0.86
1:490




0.025
4
0.77
1:160




0.05
4
0.87
1:80




0.1
4
1.07
1:40



48 hour
0.25
—
—




—
6
—




0.01
4.9
0.86
1:490




0.025
4.9
0.92
1.196




0.05
4.9
1.02
1:98


C. albicans
24 hour
5
—
—
—


ATCC # 10231

—
98
—
—




2.5
69
0.8 
1:27.6


A. niger
 7 days
20
—
—


ATCC # 16404

—
493
—




5
288
0.83
1:57.6




10
288
1.08
1:28.8





Ca = Component A (Ag-polymer formulation)


Cb = Component B (C9-C15 alkyltolylmethyltrimethylammonium chloride)




















TABLE 8








Contact







Test Organisms
Time
Ca
Cb
S.I.
Ca:Cb























P. aeruginosa
24 hour
4
—
—




ATCC # 15442

—
0.06
—





3
0.004
0.82
1:0.00133





3
0.008
0.88
1:0.00267




48 hour
7
—
—





—
0.06
—





5
0.001
0.73
1:0.0002





5
0.002
0.75
1:0.0004





5
0.004
0.78
1:0.0008





5
0.008
0.85
1:0.0016





5
0.016
0.98
1:0.0032





3
0.03
0.93
1:0.01



S. aureus
24 hour
20
—
—



ATCC # 6538)

—
0.06
—





11
0.016
0.82
1:0.00146





9
0.016
0.72
1:0.00178





9
0.03
0.95
1:0.0033





8
0.03
0.9 
1:0.00375




48 hour
20
—
—





—
0.06
—





11
0.01
0.72
1:0.0009





9
0.01
0.62
1:0.0011





9
0.03
0.95
1:0.0033



C. albicans
24 hour
30
—
—



ATCC # 10231

—
6
—





20
0.5
0.75
1:0.025





11
0.5
0.45
1:0.0455





20
1
0.83
1:0.05





11
1
0.53
1:0.091





9
1
0.47
1:0.111





11
2
0.7 
1:0.182





9
2
0.63
1:0.222





7
2
0.57
1:0.286





9
4
0.97
1:0.444





7
4
0.9 
1:0.57





5
4
0.83
1:0.8





4
4
0.8 
1:1




48 hour
30
—
—





—
6
—





11
0.5
0.45
1:0.0455





20
1
0.83
1:0.05





11
1
0.53
1:0.091





9
1
0.47
1:0.111





10
2
0.67
1:0.2





11
2
0.7 
1:0.182





9
2
0.63
1:0.222





7
2
0.57
1:0.286





9
4
0.97
1:0.444





7
4
0.9 
1:0.571





5
4
0.83
1:0.8





4
4
0.8 
1:1



A. niger
 3 days
43
—
—



ATCC # 16404

—
6
—





30
0.5
0.78
1:0.0167





30
1
0.86
1:0.033





20
2
0.8 
1:0.1





11
2
0.59
1:0.182





9
2
0.54
1:0.22





11
4
0.92
1:0.364





9
4
0.88
1:0.444





7
4
0.83
1:0.571





5
4
0.78
1:0.8




 7 days
53
—
—





—
6
—





43
0.5
0.89
1:0.0116





43
1
0.98
1:0.0233





30
2
0.9 
1:0.067





20
2
0.71
1:0.1





11
2
0.54
1:0.182





9
2
0.5 
1:0.222





11
4
0.87
1:0.364





9
4
0.84
1:0.444





7
4
0.8 
1:0.571





5
4
0.76
1:0.8







Ca = Component A - Benzisothiazolin-3-one



Cb = Component B (Ag-polymer formulation)


















TABLE 9






Contact






Test Organisms
Time
Ca
Cb
S.I.
Ca:Cb




















P. aeruginosa
24 hour
315
—
—



ATCC # 15442

—
0.06
—




255
0.004
0.88
1:0.000016




255
0.008
0.94
1.0.000031



48 hour
525
—
—




—
0.06
—




390
0.002
0.78
1:0.000005




390
0.004
0.81
1:0.00001




390
0.008
0.88
1:0.000021




315
0.016
0.87
1:0.000051




255
0.016
0.75
1:0.000063




255
0.03
0.99
1:0.000118


S. aureus
24 hour
66
—
—


ATCC # 6538

—
0.06
—




53
0.002
0.84
1:0.000038




53
0.004
0.87
1:0.000075




53
0.008
0.94
1:0.00015




39
0.008
0.72
1:0.000205




39
0.016
0.86
1:0.00041



48 hour
180
—
—




—
0.06
—




120
0.002
0.7 
1:0.000017




120
0.004
0.73
1:0.000033




120
0.008
0.8 
1:0.000067




66
0.008
0.5 
1:0.000121




120
0.016
0.93
1:0.000133




66
0.016
0.63
1:0.000242




66
0.03
0.87
1:0.000455




53
0.03
0.79
1:0.00057


C. albicans
24 hour
130
—
—


ATCC # 10231

—
6
—




105
0.5
0.89
1:0.00476




105
1
0.97
1:0.0095




85
2
0.99
1:0.0235



48 hour
130
—
—




—
6
—




85
2
0.99
1:0.02353


A. niger
 3 days
1300
—
—


ATCC # 16404

—
6
—




1050
0.5
0.89
1:0.00048




1050
1
0.97
1:0.00095




850
1
0.82
1:0.0012




850
2
0.99
1:0.00235




400
4
0.97
1:0.01



 7 days
1750
—
—




—
6
—




1300
0.5
0.83
1:0.000385




1300
1
0.91
1:0.000769




1050
2
0.93
1:0.001905





Ca = Component A (Hydrogen Peroxide)


Cb = Component B (Ag-polymer formulation)


















TABLE 10






Contact






Test Organisms
Time
Ca
Cb
S.I.
Ca:Cb




















P. aeruginosa
24 hour
0.7
—
—
—


ATCC # 15442

—
0.06
—
—




0.5
0.008
0.85
1:0.016




0.5
0.016
0.98
1:0.032



48 hour
0.9
—
—




—
0.06
—




0.7
0.008
0.91
1:0.0114


S. aureus
24 hour
0.4
—
—


ATCC # 6538

—
0.06
—




0.3
0.004
0.82
1:0.1333




0.2
0.004
0.57
1:0.02




0.3
0.008
0.88
1:0.02




0.2
0.008
0.63
1:0.04




0.2
0.016
0.77
1:0.08



48 hour
0.7
—
—




—
0.06
—




0.5
0.004
0.78
1:0.008




0.5
0.008
0.85
1:0.016




0.5
0.016
0.98
1:0.032


C. albicans
24 hour
0.9
—
—


ATCC # 10231

—
6
—




0.7
0.5
0.86
1:0.714




0.7
1
0.94
1:1.429




0.5
1
0.72
1:2




0.4
1
0.61
1:2.5




0.3
1
0.5 
1:3.3




0.2
1
0.39
1:5




0.16
1
0.34
1:6.25




0.09
1
0.27
1:11.1




0.07
1
0.24
1:14.3




0.05
1
0.22
1:20




0.5
2
0.89
1:4




0.4
2
0.78
1:5




0.3
2
0.67
1:6.67




0.2
2
0.56
1:10




0.16
2
0.51
1:12.5




0.09
2
0.43
1:22.2




0.07
2
0.41
1:28.6




0.05
2
0.39
1:40




0.04
2
0.38
1:50




0.2
4
0.89
1:20




0.16
4
0.84
1:25




0.09
4
0.77
1:44.4




0.07
4
0.74
1:57.1




0.05
4
0.72
1:80




0.04
4
0.71
1:100




0.03
4
0.7 
1:133.3




0.02
4
0.69
1:200



48 hour
2
—
—




—
6
—




1.6
0.5
0.88
1:0.313




0.9
0.5
0.53
1:0.556




1.6
1
0.97
1:0.625




0.9
1
0.62
1:1.11




0.7
1
0.52
1:1.43




0.5
1
0.42
1:2




0.4
1
0.37
1:2.5




0.3
1
0.32
1:3.33




0.2
1
0.27
1:5




0.16
1
0.25
1:6.25




0.09
1
0.21
1:11.1




0.9
2
0.78
1:2.22




0.7
2
0.68
1:2.86




0.5
2
0.58
1:4




0.4
2
0.53
1:5




0.3
2
0.48
1:6.67




0.2
2
0.43
1:10




0.16
2
0.41
1:12.5




0.09
2
0.38
1:22.22




0.5
4
0.92
1:8




0.4
4
0.87
1:10




0.3
4
0.82
1:13.3




0.2
4
0.77
1:20




0.16
4
0.75
1:25




0.09
4
0.71
1:44.4




0.07
4
0.7 
1:57.1




0.05
4
0.69
1:80




0.04
4
0.69
1:100


A. niger
 3 days
26
—
—


ATCC # 16404

—
6
—




21
0.25
0.85
1:0.012




21
0.5
0.89
1:0.024




17
0.5
0.74
1:0.029




21
1
0.97
1:0.048




17
1
0.82
1:0.059




12
1
0.63
1:0.083




17
2
0.99
1:0.118




12
2
0.79
1:0.167




8
2
0.64
1:0.25




4.4
2
0.5 
1:0.45




8
4
0.97
1:0.5




4.4
4
0.84
1:0.91




3.5
4
0.8 
1:1.14



 7 days
35
—
—




—
6
—




26
0.5
0.83
1:0.019




21
0.5
0.68
1:0.024




26
1
0.91
1:0.038




21
1
0.77
1:0.047




17
1
0.65
1:0.059




21
2
0.93
1:0.095




17
2
0.82
1:0.118




12
2
0.68
1:0.167




8
2
0.56
1:0.25




8
4
0.9 
1:0.5





Ca = as Free Cl2 Component A (Sodium hypochlorite)


Cb = Component B (Ag-polymer formulation)


















TABLE 11






Contact






Test Organisms
Time
Ca
Cb
S.I.
Ca:Cb




















P. aeruginosa
24 hour
16
—
—



ATCC # 15442

—
0.06
—




13
0.008
0.95
1:0.000615



48 hour
20
—
—




—
0.06
—




16
0.002
0.83
1:0.000125




16
0.004
0.87
1:0.00025




16
0.008
0.93
1:0.0005


S. aureus
24 hour
13
—
—


ATCC # 6538

—
0.06
—




9
0.001
0.71
1:0.00011




6
0.001
0.48
1:0.00017




9
0.002
0.73
1:0.00022




6
0.002
0.49
1:0.00033




9
0.004
0.76
1:0.00044




6
0.004
0.53
1:0.00067




3
0.004
0.3 
1:0.0013




9
0.008
0.83
1:0.00089




6
0.008
0.59
1:0.0013




3
0.008
0.36
1:0.0027




9
0.016
0.96
1:0.0018




6
0.016
0.73
1:0.0027




3
0.016
0.5 
1:0.0053




6
0.03
0.96
1:0.005




3
0.03
0.73
1:0.01




2.6
0.03
0.7 
1:0.012



48 hour
20
—
—




—
0.06
—




16
0.001
0.82
1:0.00006




13
0.001
0.67
1:0.00008




16
0.002
0.83
1:0.00013




13
0.002
0.68
1:0.00015




16
0.004
0.87
1:0.00025




13
0.004
0.72
1:0.00031




9
0.004
0.52
1:0.00044




6
0.004
0.37
1:0.00067




16
0.008
0.93
1:0.0005




13
0.008
0.78
1:0.0006




9
0.008
0.58
1:0.00089




6
0.008
0.43
1:0.00133




3
0.008
0.28
1:0.0027




13
0.016
0.92
1:0.0012




9
0.016
0.72
1:0.0018




6
0.016
0.57
1:0.0027




3
0.016
0.42
1:0.00533




9
0.03
0.95
1:0.0033




6
0.03
0.8 
1:0.005




3
0.03
0.65
1:0.01


C. albicans
24 hour
88
—
—


ATCC # 10231

—
6
—




65
0.25
0.78
1:0.0038




53
0.25
0.64
1:0.0047




65
0.5
0.82
1:0.0077




53
0.5
0.69
1:0.0094




65
1
0.91
1:0.0154




53
1
0.77
1:0.0189




43
1
0.66
1:0.0232




53
2
0.94
1:0.038




43
2
0.82
1:0.047



48 hour
88
—
—




—
6
—




65
0.25
0.78
1:0.0038




65
0.5
0.82
1:0.0077




53
0.5
0.69
1:0.0094




65
1
0.91
1:0.015




53
1
0.77
1:0.019




43
1
0.66
1:0.023




53
2
0.94
1:0.038




43
2
0.82
1:0.047


A. niger
 3 days
525
—
—


ATCC # 16404

—
6
—




425
1
0.98
1:0.0024



 7 days
650
—
—




—
6
—




525
1
0.97
1:0.0019





Ca = Component A - (Glutaraldehyde)


Cb = Component B - (Ag-polymer formulation)




















TABLE 12








Contact







Test Organisms
Time
Ca
Cb
S.I.
Ca:Cb























P. aeruginosa
24 hour
30
—
—




ATCC # 15442

—
0.06
—





20
0.008
0.8 
1:0.0004





20
0.016
0.93
1:0.0008




48 hour
43
—
—





—
0.06
—





30
0.008
0.83
1:0.00027





30
0.016
0.96
1:0.00053





20
0.03
0.97
1:0.0015



S. aureus
24 hour
9
—
—



ATCC # 6538

—
0.06
—





7
0.002
0.81
1:0.00029





7
0.004
0.84
1:0.00057





7
0.008
0.91
1:0.0011





5
0.008
0.69
1:0.0016





5
0.016
0.82
1:0.0032





4
0.03
0.94
1:0.0075





3
0.03
0.83
1:0.01




48 hour
11
—
—





—
0.06
—





9
0.001
0.83
1:0.00011





9
0.002
0.85
1:0.00022





9
0.004
0.88
1:0.00044





9
0.008
0.95
1:0.00089





7
0.016
0.9 
1:0.0023



A. niger
 3 days
9
—
—



ATCC # 16404

—
6
—





7
1
0.94
1:0.143




 7 days
30
—
—





—
6
—





20
0.5
0.75
1:0.025





20
1
0.83
1:0.05





11
2
0.7 
1:0.18





9
2
0.63
1:0.22





9
4
0.97
1:0.44





7
4
0.9 
1:0.57







Ca = Component A - 5-Chloro-2-(2,4-dichlorophenoxy)phenol



Cb = Component B (Ag-polymer formulation)


















TABLE 13






Contact






Test Organisms
Time
Ca
Cb
S.I.
Ca:Cb




















P. aeruginosa
24 hour
1050
—




ATCC # 15442

—
0.06




850
0.002
0.84
1:0.000002




850
0.004
0.88
1:0.000005




850
0.008
0.94
1:0.000009



48 hour
1300
—




—
0.06




1050
0.002
0.84
1:0.000002




1050
0.004
0.87
1:0.000004




1050
0.008
0.94
1:0.000008


S. aureus
24 hour
14
—
—


ATCC # 6538

—
0.06
—




8
0.001
0.59
1:0.00013




8
0.002
0.6 
1:0.00025




8
0.004
0.64
1:0.0005




6
0.004
0.5 
1:0.0007




8
0.008
0.7 
1:0.001




6
0.008
0.56
1:0.0013




8
0.016
0.84
1:0.002




6
0.016
0.7 
1:0.0027




6
0.03
0.93
1:0.005




5
0.03
0.86
1:0.006




4
0.03
0.79
1:0.0075




3
0.03
0.71
1:0.01



48 hour
14
—
—




—
0.06
—




8
0.001
0.59
1:0.00013




8
0.002
0.6 
1:0.00025




8
0.004
0.64
1:0.0005




6
0.004
0.5 
1:0.0007




8
0.008
0.7 
1:0.001




6
0.008
0.56
1:0.00131




8
0.016
0.84
1:0.002




6
0.016
0.7 
1:0.0027




6
0.03
0.93
1:0.005




4
0.03
0.79
1:0.0075


A. niger
 3 days
0.4
—
—


ATCC # 16404

—
6
—




0.3
1
0.92
1:3.33




0.2
1
0.67
1:5




0.2
2
0.83
1:10




0.1
4
0.92
1:40




0.08
4
0.87
1:50




0.06
4
0.82
1:66.7




0.05
4
0.79
1:80



 7 days
0.8
—
—




—
6
—




0.6
1
0.92
1:1.67




0.5
1
0.79
1:2




0.4
1
0.67
1:2.5




0.3
1
0.54
1:3.3




0.5
2
0.96
1:4




0.4
2
0.83
1:5




0.3
2
0.71
1:6.7




0.2
2
0.58
1:10




0.1
2
0.46
1:20




0.2
4
0.92
1:20




0.1
4
0.79
1:40




0.08
4
0.77
1:50




0.06
4
0.74
1:66.7




0.05
4
0.73
1:80





Ca = Component A - 3-Iodo-2-propynyl butylcarbamate


Cb = Component B (Ag-polymer formulation)

## Claims

1. A synergistic microbicidal composition; said composition comprising:
(a) a silver-containing copolymer comprising polymerized units of a monomer X and a monomer Y;

wherein the copolymer comprises 5 wt % to 11.5 wt % silver, based on total copolymer weight; and wherein monomer X is N-vinylimidazole and monomer Y comprises at least one C2-C8 alkyl (meth)acrylate; and
(b) C12-C16 alkyl dimethylbenzylammonium chloride, C9-C15 alkyltolylmethyl trimethylammonium chloride, hydrogen peroxide, or a combination thereof;
wherein a weight ratio of silver to C12-C16 alkyl dimethylbenzylammonium chloride is from 1:19.6 to 1:980, a weight ratio of silver to C9-C15 alkyltolylmethyltrimethylammonium chloride is from 1:39.2 to 1:1152 and a weight ratio of hydrogen peroxide to silver is from 1:0.000005 to 1:0.000121.

2. The composition of claim 1, wherein the copolymer comprises 6.5 wt % to 8.5 wt % silver, based on total weight of copolymer and silver.

3. The composition of claim 2, wherein the copolymer comprises 35 to 55 wt % of units derived from monomer X and 45 to 65 wt % of units derived from monomer Y.

4. The composition of claim 3, wherein monomer Y comprises n-butyl acrylate and acrylic acid.

5. The composition of claim 1 comprising the silver-containing copolymer and C12-C16 alkyl dimethylbenzylammonium chloride, C9-C15 alkyltolylmethyl trimethylammonium chloride or combinations thereof.

6. The composition of claim 5, wherein the copolymer comprises 6.5 wt % to 8.5 wt % silver, based on total weight of copolymer and silver; and wherein the copolymer comprises 35 to 55 wt % of units derived from monomer X and 45 to 65 wt % of units derived from monomer Y.

7. The composition of claim 1 comprising the silver-containing copolymer and hydrogen peroxide, wherein the copolymer comprises 6.5 wt % to 8.5 wt % silver, based on total weight of copolymer and silver; and wherein the copolymer comprises 35 to 55 wt % of units derived from monomer X and 45 to 65 wt % of units derived from monomer Y.